Covering the whole development process for the global biotechnology industry

Bioprocessing begins upstream, most often with culturing of animal or microbial cells in a range of vessel types (such as bags or stirred tanks) using different controlled feeding, aerating, and process strategies.

Beginning with harvest of material from a bioreactor, downstream processing removes or reduces contaminants to acceptable levels through several steps that typically include centrifugation, filtration, and/or chromatographic technologies.

Drug products combine active pharmaceutical ingredients with excipients in a final formulation for delivery to patients in liquid or lyophilized (freeze-dried) packaged forms — with the latter requiring reconstitution in the clinical setting.

Many technologies are used to characterize biological products, manufacturing processes, and raw materials. The number of options and applications is growing every day — with quality by design (QbD) giving impetus to this expansion.

Even as it matures, the biopharmaceutical industry is still a highly entrepreneurial one. Partnerships of many kinds — from outsourcing to licensing agreements to consultancies — help companies navigate this increasingly global business environment.

Perhaps the “hottest” buzzwords in biomanufacturing today are continuous processing and single-use technologies. They are closely related — as one is increasingly enabled by the other. Perfusion and other approaches have begun to blur the line between upstream and downstream processing (by performing certain separation/clarification duties as part of their function). And separations technology suppliers are offering solutions to the challenge of continuous drug-substance purification. Alongside a review of these advancements by BPI’s senior technical editor, contributed articles will expand on continuous upstream/production methods and continuous downstream processing technologies.

Continuous Processes: Disposables Enable the Integration of Upstream and Downstream ProcessingCheryl Scott
Continuous processing is pretty much a “given” in many other industries — such as those making chemicals and food products — and even fairly established in the larger pharmaceutical industry that makes synthetic small-molecule drugs. But the concept has only just begun to make inroads with biomanufacturers, who have until recently worked mainly in batch or fed-batch mode. Single-use technologies have largely enabled them to consider the possibility of process intensification and going continuous. BPI’s senior technical editor overviews the upstream and downstream issues, then contributors from GSK and Purifify offer a case study to “bridge the gap” between them.
The Value of Single-Use and Other Flexible Technologies in the Production of BiopharmaceuticalsDawn M. Ecker, Terence Davidovits, and Thomas C. Ransohoff (BioProcess Technology Consultants)
The high value of flexibility helps explain why single-use technologies are being increasingly adopted despite technological challenges and supplier growing pains. And it suggests why continuous processing technologies may be attractive, particularly if they can be developed in a way to maximize flexibility while keeping COGS closer to what is achievable in large conventional facilities. The authors demonstrate the value of flexibility-enabling single-use technologies that allow companies to make manufacturing decisions when demand is more certain. They present a modeling approach for quantifying that value.

Difficult-To-Express Proteins: Resolving Bioprocessing Challenges with a Scalable Perfusion BioreactorScott Waginer, Emily Wozniak, and Kyle Biesecker (The Cell Culture Company)
Among some other recombinant glycoproteins, bi- and tri-specific antibodies are labeled as “difficult-to-express” proteins because of low titers and sensitivity to environmental conditions. Traditional fed-batch culture platforms support protein production for max 3–4 weeks, with rapid loss of cell viability caused by the accumulation of waste and inconsistent nutrient availability. The authors present case studies in which difficult-to-express proteins are efficiently manufactured in perfusion hollow-fiber bioreactors, producing more concentrated protein product than could be achieved using traditional manufacturing platforms.

Is Continuous Downstream Processing of Biopharmaceuticals Becoming a Reality?Margit Holzer (Ulysse-Consult)
Separation and purification have constituted a real challenge to the continuous processing concept. The author overviews current technologies available to enable continuous downstream processing (cDSP) and describes essential development steps of unit operations as well as important factors to consider during industrial implementation. Examined technologies include in-line buffer dilution systems; continuous chromatography technologies; membrane separations/chromatography technologies and filtration; viral-inactivation methods; pumps and fluid-management systems; and flow- and pressure meters.